Mansfield, Kyle

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Department of Biochemistry and Molecular Biology

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Kyle Mansfield

Kyle Mansfield

Assistant Professor of Biochemistry & Molecular Biology

  • B.S., Ursinus College, 1994
  • Ph.D., University of Pennsylvania, 2005
  • Postdoctoral Fellowship, Duke University

Research Interests

  • Effect of Hypoxia on cellular function and gene expression
  • Posttranscriptional Regulation of gene expression
    mRNA stability, localization, translation
  • RNA Binding Proteins and their mRNA targets

Posttranscriptional Regulation During Hypoxia

Oxygen limitation, or hypoxia, is a key component of many diseases and includes periods of acute ischemia such as arise during stroke, as well as more persistent hypoxia like that which occurs in growing tumors. The ability to adapt to changes in oxygen concentration is essential for normal cell survival and recovery from ischemic conditions. This adaptation not only involves the activation of many well known transcriptional targets, but also utilizes a complementary posttranscriptional response that has not been very well studied, but likely plays a vital role in the cell’s response to hypoxia and its ability to adapt quickly to the changing environment.

Our lab is studying the cellular posttranscriptional response to hypoxia including global changes in mRNA decay and translation rates and how they relate to the severity and duration of hypoxia. We are currently focusing on the role of the HuR RNA Binding Protein (RBP) in regulating both mRNA stability and translation during hypoxic exposure. Additional studies aim to determine the cellular signaling events that lead to changes in HuR regulation and how manipulation of those signaling events can alter the cellular response to hypoxia. By understanding the posttranscriptional events that occur in hypoxic cells, we hope to better exploit these changes in designing treatments for the myriad of diseases that result in cellular hypoxia.

Selected Publications

Mansfield, K.D. and Keene, J.D. (2012) Neuron-specific ELAV/Hu proteins suppress HuR mRNA during neuronal differentiation by alternative polyadenylation. Nucleic Acids Research, 40 (6): 2734-46.

Mansfield, K.D. and Keene, J.D. (2009) The Ribonome: A Dominant Force in Coordinating Gene Expression. Biology of the Cell, 101 (3): 169-181.

Pan, Y.*, Mansfield, K.D. *, Bertozzi, C.C., Rudenko, V., Chan, D.A., Giaccia, A.J., and Simon, M.C. (2007) Multiple factors affecting cellular redox status and energy metabolism modulate HIF prolyl hydroxylase activity in vivo and in vitro. Molecular and Cellular Biology, 27 (3): 912-925. *contributed equally.

Mansfield, K.D., Guzy, R.D., Pan, Y., Young, R.M., Schumacker, P.T., and Simon, M.C. (2005) Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metabolism, 1 (6): 393-399.

Guzy, R.D., Hoyos, B., Robin, E., Chen, H., Liu, L., Mansfield, K.D., Simon, M.C., Hammerling, U. and Schumacker, P.T. (2005) Mitochondrial Complex III is required for hypoxia-induced ROS production and HIF-1α stabilization. Cell Metabolism, 1 (6): 401-408.

Selak, M.A., Armour, S.M., MacKenzie, E.D., Boulahbel, H., Watson, D.G., Mansfield, K.D., Pan, Y., Simon, M.C., Thompson, C.B., and Gottlieb, E. (2005) Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIFα prolyl hydroxylase. Cancer Cell, 7 (1): 77-85.

Mansfield, K.D., Simon, M.C., and Keith, B. (2004) Hypoxic reduction in cellular glutathione levels requires mitochondrial reactive oxygen species. Journal of Applied Physiology, 97: 1358-1366.

Contact Information

Assistant Professor of Biochemistry & Molecular Biology
Brody 5S-12
The Brody School of Medicine at East Carolina University
Greenville, NC 27834
Phone: 252.744.5519
email: mansfieldk@ecu.edu

Please use our website to learn more about our program. Feel free to contact Dr. Phillip Pekala or Dr. Brett Keiper, Associate Professor and Graduate Program Committee Chairman to see if you have what it takes to shape the future in a positive manner.

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Brody School of Medicine | Greenville, NC 27834
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